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The plant can be found all over the world and is cultivatedprimarily in South East Asian countries for its beautiful glossy heart\u2010shaped leaves, which are chewed or consumed as betelquidand widely used in Chinese and Indian folk medicine, as carminative, stimulant,astringent, against parasitic worms, conjunctivitis, rheumatism, wound, etc., andis also used for religious purposes. Hydroxychavicol is the most important bioactive compound among the wide range of phytoconstituents found in essential oil and extracts. The pharmacological attributes of<jats:italic>P<\/jats:italic>.<jats:italic>\u00a0betle<\/jats:italic>are antiproliferation, anticancer, neuropharmacological, analgesic, antioxidant, antiulcerogenic, hepatoprotective, antifertility, antibacterial, antifungal and many more. Immense attention has been paid to nanoformulations and their applications. The application of<jats:italic>P<\/jats:italic>.<jats:italic>\u00a0betle<\/jats:italic>did not show cytotoxicity in preclinical experiments, suggesting that it could serve as a promising therapeutic candidate for different diseases. The present review comprehensively summarizes the botanical description, geographical distribution, economic value and cultivation, ethnobotanical uses, preclinical pharmacological properties with insights of toxicological, clinical efficacy, and safety of<jats:italic>P<\/jats:italic>.<jats:italic>\u00a0betle<\/jats:italic>. The findings suggest that<jats:italic>P<\/jats:italic>.<jats:italic>\u00a0betle<\/jats:italic>represents an orally active and safe natural agent that exhibits great therapeutic potential for managing various human medical conditions. However, further research is needed to elucidate its underlying molecular mechanisms of action, clinical aspects, structure\u2013activity relationships, bioavailability and synergistic interactions with other drugs.<\/jats:p>","DOI":"10.1111\/jcmm.17323","type":"journal-article","created":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T06:39:10Z","timestamp":1651559950000},"page":"3083-3119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Betelvine (<i>Piper betle<\/i>L.): A comprehensive insight into its ethnopharmacology, phytochemistry, and pharmacological, biomedical and therapeutic attributes"],"prefix":"10.1111","volume":"26","author":[{"given":"Protha","family":"Biswas","sequence":"first","affiliation":[{"name":"Department of Life Sciences Presidency University Kolkata West Bengal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5924-7866","authenticated-orcid":false,"given":"Uttpal","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Ben\u2010Gurion University of the Negev Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchismita Chatterjee","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Zoology Nabadwip Vidyasagar College (Affiliated to the University of Kalyani) Nabadwip West Bengal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishi","family":"Kant","sequence":"additional","affiliation":[{"name":"Department of Biotechnology School of Health and Allied Science ARKA Jain University Jamshedpur Jharkhand India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tulika","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Botany Deen Dayal Upadhyay Gorakhpur University Gorakhpur Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harison","family":"Masih","sequence":"additional","affiliation":[{"name":"Department of Industrial Microbiology Jacob Institute of Biotechnology and Bioengineering Sam Higginbottom University of Agriculture, Technology and Sciences Prayagraj Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananya","family":"Bar","sequence":"additional","affiliation":[{"name":"Department of Zoology Wilson College (Affiliated to University of Mumbai) Mumbai Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devendra Kumar","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Lovely Professional University Phagwara Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9486-4069","authenticated-orcid":false,"given":"Niraj\u00a0Kumar","family":"Jha","sequence":"additional","affiliation":[{"name":"Department of Biotechnology School of Engineering &amp; 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